S Nakamura

Japan Atomic Energy Agency, Muramatsu, Niigata, Japan

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Publications (814)2537.1 Total impact

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    ABSTRACT: Pim-2 kinase is over-expressed in myeloma (MM) cells to enhance their growth and survival, and regarded as a novel therapeutic target in MM. However, the impact of Pim-2 inhibition on bone disease in MM remains unknown. We demonstrated here that Pim-2 expression was also up-regulated in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells in the presence of cytokines known as the inhibitors of osteoblastogenesis in MM, including IL-3, IL-7, TNF-α, TGF-β, and activin A, as well as MM cell conditioned media. The enforced expression of Pim-2 abrogated in vitro osteoblastogenesis by BMP-2, which suggested Pim-2 as a negative regulator for osteoblastogenesis. Treatment with Pim-2 siRNA as well as the Pim inhibitor SMI-16a successfully restored osteoblastogenesis suppressed by all the above inhibitory factors and MM cells. The SMI-16a treatment potentiated BMP-2-mediated anabolic signaling while suppressing TGF-β signaling. Furthermore, treatment with the newly synthesized thiazolidine-2,4-dione congener, 12a-OH, as well as its prototypic SMI-16a effectively prevented bone destruction while suppressing MM tumor growth in MM animal models. Thus, Pim-2 may play a pivotal role in tumor progression and bone loss in MM, and Pim-2 inhibition may become an important therapeutic strategy to target the MM cell-bone marrow interaction.Leukemia accepted article preview online, 02 May 2014; doi:10.1038/leu.2014.147.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 05/2014; · 10.16 Impact Factor
  • Leukemia 05/2014; · 10.16 Impact Factor
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    ABSTRACT: We studied the energy resolution of the pulsed neutron beam of the Accurate Neutron–Nucleus Reaction Measurement Instrument (ANNRI) at the Japan Proton Accelerator Research Complex/Materials and Life Science Experimental Facility (J-PARC/MLF). A simulation in the energy region from 0.7 meV to 1 MeV was performed and measurements were made at thermal (0.76−62 meV) and epithermal energies (4.8−410 eV). The neutron energy resolution of ANNRI determined by the time-of-flight technique depends on the time structure of the neutron pulse. We obtained the neutron energy resolution as a function of the neutron energy by the simulation in the two operation modes of the neutron source: double- and single-bunch modes. In double-bunch mode, the resolution deteriorates above about 10 eV because the time structure of the neutron pulse splits into two peaks. The time structures at 13 energy points from measurements in the thermal energy region agree with those of the simulation. In the epithermal energy region, the time structures at 17 energy points were obtained from measurements and agree with those of the simulation. The FWHM values of the time structures by the simulation and measurements were found to be almost consistent. In the single-bunch mode, the energy resolution is better than about 1% between 1 meV and 10 keV at a neutron source operation of 17.5 kW. These results confirm the energy resolution of the pulsed neutron beam produced by the ANNRI beamline.
    Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment 01/2014; 736:66–74. · 1.14 Impact Factor
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    ABSTRACT: IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) is characterized by serum IgG4 elevation and the infiltration of IgG4-positive plasma cells in glandular tissues. For definitive diagnosis of IgG4-DS, biopsies of local lesions are recommended to exclude Sjögren's syndrome (SS), malignant tumours, and similar disorders. In this study, we examined the diagnostic utility of submandibular gland (SMG) and labial salivary gland (LSG) biopsies in IgG4-DS. Fourteen patients presenting with swelling of the SMG (eight females and six males) underwent both SMG and LSG biopsies. The sensitivity, specificity, and accuracy of SMG biopsies were all 100.0%. In contrast, those of LSG biopsies were 69.2%, 100.0%, and 71.4%, respectively. Thirty-three out of 61 LSG biopsies (54.1%) from all 14 patients were positive for the diagnostic criteria of IgG4-DS (IgG4-positive/IgG-positive plasma cells >0.4). None of the patients experienced complications such as facial nerve palsy, sialocele, or hyposalivation. The IgG4/IgG ratio showed no significant correlation between the LSG and SMG. The final diagnosis was IgG4-DS in 13 patients and marginal zone B-cell lymphoma (MZL) in one. These results suggest that incisional biopsy of the SMG is useful and appropriate for the definitive diagnosis of IgG4-DS, while diagnosis by LSG biopsy alone requires more caution.
    International Journal of Oral and Maxillofacial Surgery 01/2014; · 1.52 Impact Factor
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    ABSTRACT: A nuclear data project entitled “Systematic Study on Neutron Capture Reaction Cross Sections for the Technological Development of Nuclear Transmutation of Long-Lived Nuclear Wastes” is being performed. The objective of the project is to improve nuclear data libraries, by making the precise measurements of neutron capture cross sections of Long-Lived Nuclear Wastes (LLNWs), analyzing the measured results theoretically, and supplying reliable calculated capture cross sections for the LLNWs. This contribution presents the outline of the project, and individual results are presented by other contributions.
    Nuclear Data Sheets. 01/2014; 118:72–77.
  • M. Koizumi, J. Goto, S. Matsuki, S. Nakamura
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    ABSTRACT: Dynamic nuclear self-polarization (DYNASP) is a phenomenon observed in III-V semiconductors. When electrons of the valence band of a semiconductor are optically excited to the conduction band, a relaxation process of the conduction electrons induces a large nuclear polarization to suddenly occur below a critical temperature. This mechanism is useful for nuclear magnetic moment measurements of unstable nuclei implanted in semiconductors.
    Nuclear Instruments and Methods in Physics Research Section B Beam Interactions with Materials and Atoms 12/2013; · 1.27 Impact Factor
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    ABSTRACT: This randomized, multicenter study compared the efficacy of docetaxel with or without capecitabine following fluorouracil/epirubicin/cyclophosphamide (FEC) therapy in operable breast cancer and investigated the role of Ki67 as a predictive biomarker. Patients were randomized to 4 cycles of docetaxel/capecitabine (docetaxel: 75 mg/m(2) on day 1; capecitabine: 1,650 mg/m(2) on days 1-14 every 3 weeks) or docetaxel alone (75 mg/m(2) on day 1 every 3 weeks) after completion of 4 cycles of FEC (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2) on day 1 every 3 weeks). The primary endpoint was the pathological complete response (pCR) rate. Predictive factor analysis was conducted using clinicopathological markers, including hormone receptors and Ki67 labeling index (Ki67LI). A total of 477 patients were randomized; the overall response in the docetaxel/capecitabine and docetaxel groups was 88.3 and 87.4 %, respectively. There were no significant differences in the pCR rate (docetaxel/capecitabine: 23 %; docetaxel: 24 %; p = 0.748), disease-free survival, or overall survival. However, patients with mid-range Ki67LI (10-20 %) showed a trend towards improved pCR rate with docetaxel/capecitabine compared to docetaxel alone. Furthermore, multivariate logistic regression analysis showed pre-treatment Ki67LI (odds ratio 1.031; 95 % CI 1.014-1.048; p = 0.0004) to be a significant predictor of pCR in this neoadjuvant treatment setting. Docetaxel/capecitabine (after 4 cycles of FEC) did not generate significant improvement in pCR compared to docetaxel alone. However, exploratory analyses suggested that assessment of pre-treatment Ki67LI may be a useful tool in the identification of responders to preoperative docetaxel/capecitabine in early-stage breast cancer.
    Breast Cancer Research and Treatment 10/2013; · 4.47 Impact Factor
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    ABSTRACT: Background:For patients with breast cancer treated with preoperative chemotherapy, residual tumour burden in lymph nodes is the strongest prognostic factor. However, conventional pathological examination has limitations that hinder the accurate and reproducible measurement. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method for detecting nodal metastasis. In this prospective multicentre trial, we assessed the performance of the OSNA assay in detecting nodal metastasis after chemotherapy.Methods:In total, 302 lymph nodes from 80 breast cancer patients who underwent axillary dissection after chemotherapy were analysed. Each node was cut into two or four slices. One piece or alternate pieces were evaluated by pathology, and the other(s) were examined using the OSNA assay. The results of the two methods were compared. Stromal fibrosis, histiocytic aggregates, and degenerated cancer cells were regarded as chemotherapy-induced histological changes.Results:The overall accuracy, sensitivity, and specificity of the OSNA assay compared with the reference pathology were 91.1%, 88.3%, and 91.7%, respectively. Of the 302 lymph nodes, 66 (21.9%) exhibited chemotherapy-induced histology. For these nodes, the accuracy, sensitivity, and specificity were 90.9%, 88.9%, and 93.3%, respectively.Conclusion:The OSNA assay can detect the residual tumour burden as accurately as conventional pathology, although chemotherapy-induced histological changes are present.British Journal of Cancer advance online publication, 3 September 2013; doi:10.1038/bjc.2013.503 www.bjcancer.com.
    British Journal of Cancer 09/2013; · 5.08 Impact Factor
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    ABSTRACT: The proteasome inhibitor bortezomib has revolutionized the treatment of multiple myeloma. However, bortezomib-induced peripheral neuropathy (BiPN) is a serious complication that compromises clinical outcome. If patients with a risk of developing BiPN could be predicted, physicians might prefer weekly, reduced-dose, or subcutaneous approaches. To seek biomarkers for BiPN, we conducted a multicenter prospective study using a simple and unique system. Multiple myeloma patients received twice-weekly or weekly 1.3 mg/m(2) bortezomib intravenously, and a 2-ml sample of whole blood was obtained before treatment and 2-3 days and 1-3 weeks after the first dose. Induction of gene expression was then quantified by real-time PCR. Of a total of 64 enrolled patients, 53 patient samples qualified for mRNA analysis. The BiPN grade was associated with phytohemagglutinin-induced IL2, IFNG and TNFSF2, as well as with lipopolysaccharide-induced IL6 levels. More importantly, of the 19 patients showing a 3-fold increase in phytohemagglutinin-induced IL2, 14 did not suffer from BiPN (73.7% prediction), whereas of the 34 patients with a <3-fold increase, 23 experienced BiPN (67.6% prediction). Therefore, we concluded that pretreatment of phytohemagglutinin-induced IL2 mRNA levels in whole blood serve as a promising biomarker for predicting BiPN, and this finding warrants validation in a larger study.
    Blood Cancer Journal 01/2013; 3:e150. · 1.40 Impact Factor
  • Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 11/2012; · 10.16 Impact Factor
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    ABSTRACT: For trans-uranium elements, stable atomic isobars do not exist. In order to provide isobaric reference ions for the mass measurement of trans-uranium elements, an electrospray ion source (ESI) was combined with an rf-carpet to collect molecular ions efficiently. The rf-carpet allows for simplification of the pumping system to transport ions from the ESI to a precision mass analyzer. Molecular ions appropriate for isobaric references of trans-uranium elements were extracted from the rf-carpet and analyzed by a multi-reflection time-of-flight mass spectrograph (MRTOF-MS) with a resolving power of $\rm{R_m} \gtrsim100,000$.
    International Journal of Mass Spectrometry. 11/2012; 337.
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    ABSTRACT: A new laser ion source configuration based on resonant photoionization in a gas cell has been developed at RIBF RIKEN. This system is intended for the future PArasitic RI-beam production by Laser Ion-Source (PALIS) project which will be installed at RIKEN's fragment separator, BigRIPS. A novel implementation of differential pumping, in combination with a sextupole ion beam guide (SPIG), has been developed. A few small scroll pumps create a pressure difference from 1000 hPa - 10^-3 Pa within a geometry drastically miniaturized compared to conventional systems. This system can utilize a large exit hole for fast evacuation times, minimizing the decay loss for short-lived nuclei during extraction from a buffer gas cell, while sufficient gas cell pressure is maintained for stopping high energy RI-beams. In spite of the motion in a dense pressure gradient, the photo-ionized ions inside the gas cell are ejected with an assisting force gas jet and successfully transported to a high-vacuum region via SPIG followed by a quadrupole mass separator. Observed behaviors agree with the results of gas flow and Monte Carlo simulations.
    Nuclear Instruments and Methods in Physics Research Section B Beam Interactions with Materials and Atoms 10/2012; 295. · 1.27 Impact Factor
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    ABSTRACT: High-spin states in 173W have been studied using the 150Nd(28Si,5n)173W reaction at beam energies of 135 and 140 MeV. The previously known bands associated with the 7/2+[633], 5/2−[512], and 1/2−[521] configurations are extended significantly, and the unfavored signature branch of the 1/2−[521] band is established for the first time. The band properties, such as level spacings, band-crossing frequencies, alignment gains, and signature splittings, are discussed with an emphasis on the low-spin signature inversion observed in the 5/2−[512] band. By comparing the experimental B(M1)/B(E2) ratios with the theoretical values, we conclude that the configuration of the 5/2−[512] band is quite pure at low spins without appreciable admixture of the 5/2−[523] orbit, in conflict with the particle rotor model calculated results.
    Physical Review C 10/2012; 86(4). · 3.72 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the initiation and progression of autoimmune damage in the lesions of labial salivary glands (LSGs) from primary Sjögren's syndrome (SS) patients by examining the selective localization of T helper (Th) subsets such as Th1, Th2, Th17 regulatory T cells (T(regs)) and follicular T helper cells (Tfh). The expression of cytokines and transcription factors associated with these Th subsets in the LSGs from 54 SS patients and 16 healthy controls was examined using real-time polymerase chain reaction (PCR) and immunostaining. Additionally, infiltrating lymphocytes without germinal centre (GC(-)) and with GC (GC(+)) in the LSGs specimens from eight SS patients were extracted selectively by laser capture microdissection (LCM). The mRNA expression of these molecules was compared between the two sample groups of GC(-) and GC(+) by real-time PCR. The mRNA expression of cytokines and transcription factors of all T helper (Th) subsets in the LSGs from the SS patients was increased significantly in comparison with controls. In LSGs from the SS patients, Th2 and Tfh was associated closely with strong lymphocytic infiltration; however, Th1, Th17 and T(regs) was not. In the selectively extracted lesions of LSGs, Th1 and Th17-related molecules were detected strongly in the GC(-), while Th2 and Tfh-related molecules were detected in the GC(+). In contrast, no significant association with strong lymphocytic infiltration was observed in T(reg)-related molecules. These results indicate that SS has selective localization of Th subsets such as Th1, Th2, Th17 and Tfh in the LSGs, which is associated closely with disease severity and/or status. SS might be initiated by Th1 and Th17 cells, and then progressed by Th2 and Tfh cells via GC formation.
    Clinical & Experimental Immunology 08/2012; 169(2):89-99. · 3.41 Impact Factor
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    ABSTRACT: To investigate the pathogenesis of localized autoimmune damage in Sjögren's syndrome (SS) by examining the expression patterns of cytokines, chemokines and chemokine receptors at sites of autoimmune damage. mRNA expression of these molecules in the labial salivary glands (LSGs) and peripheral blood mononuclear cells (PBMCs) from 36 SS patients was examined using a real-time polymerase chain reaction-based method. Subsets of the infiltrating lymphocytes and chemokines/chemokine receptors expression in the LSG specimens were examined by immunohistochemistry. Cytokines/chemokine concentrations in the saliva were analysed using flow cytometry or enzyme-linked immunosorbent assay. mRNA expression of T helper type 1 (Th1) cytokines, chemokines and chemokine receptors was higher in LSGs than in PBMCs. In contrast, mRNA expression of Th2 cytokines, chemokines [thymus and activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine (MDC/CCL22)] and chemokine receptor (CCR4) was associated closely with strong lymphocytic accumulation in LSGs. Furthermore, TARC and MDC were detected immunohistochemically in/around the ductal epithelial cells in LSGs, whereas CCR4 was detected on infiltrating lymphocytes. The concentrations of these cytokines/chemokines were significantly higher in the saliva from SS patients than those from controls, and the concentrations of Th2 cytokines/chemokines were associated closely with strong lymphocytic accumulation in LSGs. These results suggest that SS might be initiated and/or maintained by Th1 and Th17 cells and progress in association with Th2 cells via the interaction between particular chemokines/chemokine receptors. Furthermore, the measurement of cytokines/chemokines in saliva is suggested to be useful for diagnosis and also to reveal disease status.
    Clinical & Experimental Immunology 07/2012; 169(1):17-26. · 3.41 Impact Factor
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    ABSTRACT: Chronic GVHD (cGVHD) after allogeneic hematopoietic SCT (HSCT) is characterized by an infiltration of T cells into target organs including the oral mucosa and salivary glands. This study was designed to clarify the molecular mechanism of the local accumulation of pathogenic T cells in cGVHD. The expression of cytokines, chemokines and chemokine receptors in the buccal mucosa (BM), labial salivary glands (LSG) and PBMC from 16 patients with cGVHD after allogeneic HSCT was examined. The mRNA expression of T helper 1 (Th1) and Th2 cytokines, and several chemokines and chemokine receptors was significantly increased in the BM and LSG from cGVHD patients, in comparison with both those in the BM and LSG from controls, respectively, and also with those in the PBMC from cGVHD patients. Furthermore, the mRNA expression of Th2 cytokines, macrophage-derived chemokine and CC chemokine receptor 4 was closely associated with a strong T-cell infiltration in the BM and LSG from cGVHD patients. These results suggest that cGVHD might be initiated and/or maintained by Th1/Th0 cells and thereafter progresses in association with Th2 cell accumulation via the interaction of particular chemokine and chemokine receptors.Bone Marrow Transplantation advance online publication, 4 June 2012; doi:10.1038/bmt.2012.100.
    Bone marrow transplantation 06/2012; · 3.00 Impact Factor
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    ABSTRACT: Background Clinical features and outcomes of extranodal natural killer/T-cell lymphoma (ENKL) arising from extranasal sites are not fully understood. The purpose of this study was to study the prognosis and treatment outcome of skin/soft tissue primary ENKL. Patients and methods This multicenter retrospective study included 48 patients with skin/soft tissue primary ENKL diagnosed from 1993 to 2010. Results Patients with Ann Arbor stage I, T1-2N0M0 by International Society for Cutaneous Lymphomas-European Organization of Research and Treatment of Cancer TNM (tumour-node-metastasis) stage, International prognostic index score of 0-1, and a Korean prognostic index (KPI) score of 0-1 were associated with better survival. Four of five patients with T1-2N0M0 disease achieved complete response with radiation alone. In disseminated disease, only 6 of 13 patients responded to anthracycline-containing chemotherapy, and all the two patients receiving SMILE showed response. Conclusion In conclusion, we identified the prognostic value of KPI, and we suggest a treatment recommendation according to the TNM (tumour-node-metastasis) stage. Radiotherapy with/without chemotherapy seemed to be optimal in localized disease. In advanced stages, a more aggressive treatment regimen with newer agents should be sought.
    Annals of Oncology 04/2012; 23(10):2703-7. · 7.38 Impact Factor
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    ABSTRACT: Cancer stem cells have been proposed to be responsible for tumorigenesis and recurrence in various neoplastic diseases, including multiple myeloma (MM). We have previously reported that MM cells specifically express HLA class I at high levels and that single-chain Fv diabody against this molecule markedly induces MM cell death. Here we investigated the effect of a new diabody (C3B3) on cancer stem cell-like side population (SP) cells. SP fraction of MM cells highly expressed ABCG2 and exhibited resistance to chemotherapeutic agents; however, C3B3 induced cytotoxicity in both SP cells and main population (MP) cells to a similar extent. Moreover, C3B3 suppressed colony formation and tumorigenesis of SP cells in vitro and in vivo. Crosslinking of HLA class I by C3B3 mediated disruption of lipid rafts and actin aggregation, which led to inhibition of gene expression of β-catenin and pluripotency-associated transcription factors such as Sox2, Oct3/4 and Nanog. Conversely, knockdown of Sox2 and Oct3/4 mRNA reduced the proportion of SP cells, suggesting that these factors are essential in maintenance of SP fraction in MM cells. Thus, our findings reveal that immunotherapeutic approach by engineered antibodies can overcome drug resistance, and provide a new basis for development of cancer stem cell-targeted therapy.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 03/2012; 26(9):2124-34. · 10.16 Impact Factor

Publication Stats

13k Citations
2,537.10 Total Impact Points

Institutions

  • 2006–2014
    • Japan Atomic Energy Agency
      • Nuclear Science and Engineering Directorate
      Muramatsu, Niigata, Japan
  • 1974–2014
    • Kyushu University
      • • Faculty of Dental Science
      • • Department of Clinical Medicine
      • • Department of Oral and Maxillofacial Surgery
      • • Faculty of Medical Sciences
      Hukuoka, Fukuoka, Japan
  • 2013
    • Japanese Foundation for Cancer Research
      Edo, Tōkyō, Japan
  • 2009–2013
    • St. Luke's International Hospital
      Edo, Tōkyō, Japan
    • Hyogo College of Medicine
      • Department of Gastroenterology
      Nishinomiya, Hyogo-ken, Japan
  • 1999–2013
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
    • Tokyo Women's Medical University
      • Department of Neurosurgery
      Tokyo, Tokyo-to, Japan
    • Osaka Red Cross Hospital
      Ōsaka, Ōsaka, Japan
    • The Graduate University for Advanced Studies
      • Department of Information Physiology
      Miura, Kanagawa-ken, Japan
    • University of the Ryukyus
      • First Department of Internal Medicine
      Okinawa, Okinawa-ken, Japan
  • 2012
    • University of Tsukuba
      Tsukuba, Ibaraki, Japan
  • 2011
    • Showa University
      Shinagawa, Tōkyō, Japan
  • 1984–2011
    • Kyoto University
      • • Department of Breast Surgery
      • • Research Reactor Institute
      • • Department of Neurology
      Kyoto, Kyoto-fu, Japan
  • 2010
    • Institute for Environmental Sciences
      Ōmisawa, Aomori Prefecture, Japan
  • 1999–2010
    • Dokkyo Medical University
      • Department of Anatomic and Diagnostic Pathology
      Tochigi, Tochigi-ken, Japan
  • 1991–2009
    • Hiroshima University
      • • Faculty of Medicine
      • • School of Medicine
      Hiroshima-shi, Hiroshima-ken, Japan
    • Japan Women's University
      Edo, Tōkyō, Japan
  • 2008
    • The Corporation for Production and Research of Laboratory Primates
      Tsukuba, Ibaraki, Japan
  • 1999–2008
    • Aichi Medical University
      • Department of Pathology
      Japan
  • 1989–2008
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 1986–2008
    • Nagoya University
      • • Clinical Laboratory
      • • Division of Pathology
      Nagoya, Aichi, Japan
    • Rakuwakai Otowa Hospital
      Kioto, Kyōto, Japan
  • 2007
    • Toranomon Hospital
      Edo, Tōkyō, Japan
  • 2005–2007
    • Gunma Prefectural Cancer Center
      Maebashi, Gunma Prefecture, Japan
  • 2000–2005
    • Kumamoto University
      • Department of Cardiovascular Medicine
      Kumamoto, Kumamoto Prefecture, Japan
    • Kumamoto Kinoh Hospital
      Kumamoto, Kumamoto Prefecture, Japan
    • Nippon Veterinary and Animal Science University
      • Department of Veterinary Pathology
      Edo, Tōkyō, Japan
  • 1988–2005
    • Osaka City University
      • • Department of Gastroenterology
      • • Third Department of Internal Medicine
      Ōsaka, Ōsaka, Japan
  • 2003
    • Fujita Health University
      • Department of Oral and Maxillo-facial Surgery
      Nagoya, Aichi, Japan
  • 2002
    • Nagoya City University
      • Department of Internal Medicine
      Nagoya, Aichi, Japan
  • 2001
    • Kobe City Medical Center General Hospital
      Kōbe, Hyōgo, Japan
    • Matsuyama Red Cross Hospital
      Matuyama, Ehime, Japan
    • Otsuka Pharmaceutical Group
      Edo, Tōkyō, Japan
    • Hokkaido University
      • Department of Internal Medicine II
      Sapporo-shi, Hokkaido, Japan
    • Chiba University
      • Department of Radiology
      Chiba-shi, Chiba-ken, Japan
    • The University of Tokushima
      • Department of Clinical Neuroscience
      Tokusima, Tokushima, Japan
    • Kurashiki Central Hospital
      • Department of Neurology
      Kurasiki, Okayama, Japan
  • 2000–2001
    • Sophia University
      • Division of Electrical and Electronics Engineering
      Tokyo, Tokyo-to, Japan
  • 1998–2001
    • Kyoto Prefectural University of Medicine
      Kioto, Kyōto, Japan
    • Aichi Prefectural Institute of Public Health
      Nagoya, Aichi, Japan
    • Gifu Prefectural Tajimi Hospital
      Gihu, Gifu, Japan
  • 1995–2001
    • The University of Tokyo
      • Faculty and Graduate School of Agriculture and Life Sceince
      Tokyo, Tokyo-to, Japan
  • 1997–1999
    • Juntendo University
      • Department of Neurology
      Tokyo, Tokyo-to, Japan
    • Akita University Hospital
      Akita, Akita, Japan
    • National Institute of Agrobiological Sciences
      Tsukuba, Ibaraki, Japan
  • 1994–1999
    • National Cerebral and Cardiovascular Center
      Ōsaka, Ōsaka, Japan
  • 1993–1999
    • Yokohama City University
      • • Department of Medicine
      • • Department of Dermatology (YCUH)
      Yokohama, Kanagawa, Japan
    • North Internal Medicine
      Bartlett, Tennessee, United States
    • Japan BCG Laboratory
      Edo, Tōkyō, Japan
  • 1996–1997
    • Toyama University
      Тояма, Toyama, Japan
    • Nagasaki University Hospital
      Nagasaki, Nagasaki, Japan
    • Tenri Yorozu Hospital
      Тэнри, Nara, Japan
    • National Center of Neurology and Psychiatry
      • Department of Biochemistry and Cellular Biology
      Кодаиры, Tōkyō, Japan
  • 1995–1997
    • NEC Corporation
      Edo, Tōkyō, Japan
  • 1985–1994
    • Kanazawa University
      • School of Medicine
      Kanazawa, Ishikawa, Japan
  • 1980–1993
    • Tohoku University
      • • Department of Pathology
      • • Department of Chemistry
      Sendai, Kagoshima, Japan
  • 1992
    • Ja Hiroshima General Hospital
      Hirosima, Hiroshima, Japan